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来源:BMC Infectious Diseases

作者:Helmut Ostermann;Kyle McBride;Jesús Medina;等

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Background The treatment of complicated skin and soft tissue infections (cSSTI) is challenging and many patients do not receive adequate first-line therapy. REACH (REtrospective Study to Assess the Clinical Management of Patients With Moderate-to-Severe cSSTI or Community-Acquired Pneumonia in the Hospital Setting) was a retrospective observational study of cSSTI patients in real-life settings in European hospitals. In this analysis, we review characteristics and outcomes of patients with an early response (≤72 hours) compared with those without an early response to treatment. We also compare the results according to two differing definitions of early response, one of which (Definition 1) requires resolution of fever within 72 hours, in line with previous US FDA guidelines. Methods Patients were adults hospitalized with cSSTIs 2010–2011 and requiring treatment with intravenous antibiotics. Clinical management, clinical outcomes and healthcare resource use were assessed using a descriptive analysis approach. Results The analysis set included 600 patients, of which 363 showed early response with Definition 1 and 417 with Definition 2. Initial treatment modification was frequent, and highest in patients without early response (48.1% with Definition 1). Patients without early response were more likely to have diabetes than those with early response (31.6% vs. 22.9%, respectively) and to suffer from more severe disease (e.g. skin necrosis: 14.8% and 7.7%, respectively), to be infected with difficult-to-treat microorganisms and to have recurrent infections. Furthermore, patients without early response had a higher rate of adverse clinical outcomes (e.g. septic shock) and higher use of healthcare resources. The results obtained with the two definitions for early response were largely similar. Conclusions This study highlights the significance of early evaluation of patients in hospitals, in potentially preventing prolonged use of inappropriate or ineffective antibacterial therapy. Trial registration NCT01293435.

    来源:BMC Infectious Diseases

    作者:Dean B. Everett;Robert S. Heyderman;Neil French;等

    关键词:Multiple carriage;Capsule biosynthesis;...

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    Background

    Carriage of either single or multiple pneumococcal serotypes (multiple carriage) is a prerequisite for developing invasive pneumococcal disease. However, despite the reported high rates of pneumococcal carriage in Malawi, no data on carriage of multiple serotypes has been reported previously. Our study provides the first description of the prevalence of multiple pneumococcal carriage in Malawi.

    Methods

    The study was conducted in Blantyre and Karonga districts in Malawi, from 2008 to 2012. We recruited 116 children aged 0–13 years. These children were either HIV-infected (N = 44) or uninfected (N = 72). Nasopharyngeal samples were collected using sterile swabs. Pneumococcal serotypes in the samples were identified by microarray. Strains that could not be typed by microarray were sequenced to characterise possible genetic alterations within the capsular polysaccharide (CPS) locus.

    Results

    The microarray identified 179 pneumococcal strains (from 116 subjects), encompassing 43 distinct serotypes and non-typeable (NT) strains. Forty per cent (46/116) of children carried multiple serotypes. Carriage of vaccine type (VT) strains was higher (p = 0.028) in younger (0–2 years) children (71 %, 40/56) compared to older (3–13 years) children (50 %, 30/60). Genetic variations within the CPS locus of known serotypes were observed in 19 % (34/179) of the strains identified. The variants included 13-valent pneumococcal conjugate vaccine (PCV13) serotypes 6B and 19A, and the polysaccharide vaccine serotype 20. Serotype 6B variants were the most frequently isolated (47 %, 16/34). Unlike the wild type, the CPS locus of the 6B variants contained an insertion of the licD-family phosphotransferase gene. The CPS locus of 19A- and 20-variants contained an inversion in the sugar-biosynthesis (rmlD) gene and a 717 bp deletion within the transferase (whaF) gene, respectively.

    Conclusions

    The high multiple carriage in Malawian children provides opportunities for genetic exchange through horizontal gene transfer. This may potentially lead to CPS locus variants and vaccine escape. Variants reported here occurred naturally, however, PCV13 introduction could exacerbate the CPS genetic variations. Further studies are therefore recommended to assess the invasive potential of these variants and establish whether PCV13 would offer cross-protection. We have shown that younger children (0–2 years) are a reservoir of VT serotypes, which makes them an ideal target for vaccination.

      来源:BMC Infectious Diseases

      作者:Naomi S Levitt;Robert J Wilkinson;Nuala McGrath;等

      关键词:Multimorbidity;Diabetes;...

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      Background

      Many low and middle-income countries are experiencing colliding epidemics of chronic infectious (ID) and non-communicable diseases (NCD). As a result, the prevalence of multiple morbidities (MM) is rising.

      Methods

      We conducted a study to describe the epidemiology of MM in a primary care clinic in Khayelitsha. Adults with at least one of HIV, tuberculosis (TB), diabetes (DM), and hypertension (HPT) were identified between Sept 2012-May 2013 on electronic databases. Using unique patient identifiers, drugs prescribed across all facilities in the province were linked to each patient and each drug class assigned a condition.

      Results

      These 4 diseases accounted for 45% of all prescription visits. Among 14364 chronic disease patients, HPT was the most common morbidity (65%). 22.6% of patients had MM, with an increasing prevalence with age; and a high prevalence among younger antiretroviral therapy (ART) patients (26% and 30% in 18-35 yr and 36–45 year age groups respectively). Among these younger ART patients with MM, HPT and DM prevalence was higher than in those not on ART.

      Conclusions

      We highlight the co-existence of multiple ID and NCD. This presents both challenges (increasing complexity and the impact on health services, providers and patients), and opportunities for chronic diseases screening in a population linked to care. It also necessitates re-thinking of models of health care delivery and requires policy interventions to integrate and coordinate management of co-morbid chronic diseases.

        来源:BMC Infectious Diseases

        作者:Álvaro Luiz Bertho;Alda Maria Da-Cruz;Cláudia M Valete-Rosalino;等

        关键词:Leishmania braziliensis;During antimonial treatment;...

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        Background

        Leishmaniasis is an important parasitic disease affecting millions worldwide. Human cutaneous leishmaniasis (CL) is endemic in Rio de Janeiro, Brazil, where is caused by Leishmania braziliensis. The adaptive immune response is accountable for the healing of CL and despite of key role of CD8+ T cells in this immune response little is known about the CD8+ T lymphocytes frequencies, apoptosis and antigen-responsive CD8+ T lymphocytes of CL patients during antimonial therapy.

        Methods

        Using flow cytometry, we examined total and effector CD8+ T cells from CL patients before (PBT), during (PDT) and after (PAT) treatment for apoptosis and frequencies upon isolation and after in vitro L. braziliensis antigens (LbAg)-stimulation culture. Besides, a correlation study between immunological findings and lesion size was done.

        Results

        PDT showed lower frequencies of total CD8+ T lymphocytes and higher levels of apoptosis of these cells, which were also observed following LbAg-stimulation culture. Regarding effector CD8+ T cells, high frequencies were observed in PDT, while lower frequencies were observed in PAT. Interestingly, PDT showed higher frequencies of apoptotic-effector CD8+ T lymphocytes. Similar results were seen after in vitro antigenic-stimulation assays. Correlation analysis showed that the greater the size of lesion, the smaller the frequency of effector CD8+ T lymphocytes in PDT and PAT, as well as a positive correlation between apoptotic-effector CD8+ T cells frequency and lesion size of PDT.

        Conclusions

        Changes in effector CD8+ T–lymphocyte frequencies, during and after treatment, seem to represent a critical stage to generate an efficient immune response and suggest that these cells would be evolved in the triggering or in the resolution of lesion, under the influence of therapy. This hypothesis opens new perspectives to clarify controversial statements about the protective or deleterious role of CD8+ T cells in the cure or aggravation of CL and the new approach of evaluating patients during treatment proved to be of utmost importance for understanding the immune response in the healing process of human CL.

          来源:BMC Infectious Diseases

          作者:Corinne Levy;Emmanuelle Varon;Stéphane Bonacorsi;等

          关键词:Haemophilus influenzae;Betalactamase;...

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          Background

          After the implementation of pneumococcal conjugate vaccines (PCVs), the marked shift in Streptococcus pneumoniae (Pnc) serotype distribution led to a modification in pneumococcal antibiotic susceptibility. In 2011, the pattern of antibiotic prescription in France for acute otitis media in infants was greatly modified, with decreased use of third-generation cephalosporins and amoxicillin–clavulanate replaced by amoxicillin alone. To assess antibiotic strategies, here we measured the antibiotic susceptibility of Pnc and Haemophilus influenzae (Hi) isolated from nasopharyngeal flora in infants with acute otitis media in the 13-valent PCV (PCV13) era in France.

          Methods

          From November 2006 to June 2013, 77 pediatricians obtained nasopharyngeal swabs from infants (6 to 24 months old) with acute otitis media. The swabs were sent for analysis to the national reference centre for pneumococci in France. Demographics, medical history, and physical examination findings were recorded.

          Results

          We examined data for 7200 children, 3498 in the pre-PCV13 period (2006–2009) and 3702 in the post-PCV13 period (2010–2013). The Pnc carriage rate decreased from 57.9 % to 54.2 % between the 2 periods, and the proportion of pneumococcal strains with reduced susceptibility to penicillin or resistant to penicillin decreased from 47.1 % to 39 % (P < 0.0001). The Hi carriage rate increased from 48.2 % to 52.4 %, with the proportion of ß-lactamase–producing strains decreasing from 17.1 % to 11.9 % and the proportion of ß-lactamase–nonproducing, ampicillin-resistant strains remaining stable, from 7.7 % to 8.2 %. We did not identify any risk factor associated with carriage of ß-lactamase–producing Hi strains (such as daycare center attendance, otitis-prone condition or recent antibiotic use).

          Conclusion

          In France, the nasopharyngeal carriage rate of reduced-susceptibility pneumococcal strains and ß-lactamase–producing Hi strains decreased in children with acute otitis media after 2010, the year the PCV13 was introduced. Accordingly, amoxicillin as the first-line drug for acute otitis media requiring antibiotics remains a valid choice.

            来源:BMC Infectious Diseases

            作者:Ole Wichmann;Birte Bödeker;Thorsten Rieck;等

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            Background Elderly people are at increased risk for severe influenza illness and constitute therefore a major target-group for seasonal influenza vaccination in most industrialized countries. The aim of this study was to estimate influenza vaccine effectiveness (VE) among individuals aged 60+ years over three seasons and to assess if the screening method is a suitable tool to monitor influenza VE in this particular target-group in Germany. Methods We identified laboratory-confirmed influenza cases aged 60+ years through the national communicable disease reporting system for seasons 2010/11, 2011/12 and 2012/13. Vaccination coverage (VC) data were retrieved from a database of health insurance claims representing ~85% of the total German population. We applied the screening method to calculate influenza subtype-specific VE and compared our results with VE estimates from other observational studies in Europe. Results In total, 7,156 laboratory-confirmed influenza cases were included. VE against all influenza types ranged between 49% (95% confidence interval [CI]: 39–56) in 2011/12 and 80% (95%CI: 76-83%) in 2010/11. In 2010/11 subtype-specific VE against influenza A(H1N1)pdm and B was 76% and 84%, respectively. In the following seasons, VE against influenza A(H1N1)pdm, A(H3N2) and B was 87%, -9% , 74% (2011/12), and 74%, 39%, 73% (2012/13). VE was higher among hospitalized compared to non-hospitalized influenza A cases. Seventeen observational studies from Europe reporting subtype-specific VE among the elderly were identified for the respective seasons (all applying the test-negative design) and showed comparable subtype-specific VE estimates. Conclusions According to our study, influenza vaccination provided moderate protection against laboratory-confirmed influenza A(H1N1)pdm and B in individuals aged 60+ but no or only little protection against A(H3N2). Higher VE among hospitalized cases might indicate higher protection against severe influenza disease. Based on the available data, the screening method allowed us to assess subtype-specific VE in hospitalized and non-hospitalized elderly persons. Since controlling for several important confounders was not possible, the applied method only provided crude VE estimates. However, given the precise VC-data and the large number of cases, the screening method provided results being in line with VE estimates from other observational studies in Europe that applied a different study design.